Date Published: March 15, 2019
Publisher: Public Library of Science
Author(s): Hoda Gad, Adnan Khan, Naveed Akhtar, Saadat Kamran, Ahmed El-Sotouhy, Soha R. Dargham, Ioannis N. Petropoulos, Georgios Ponirakis, Ashfaq Shuaib, Leopold J. Streletz, Rayaz A. Malik, Masaki Mogi.
To determine if corneal confocal microscopy can identify corneal nerve and endothelial cell abnormalities and may be useful in the prognostication of patients with transient ischemic attack  or minor ischemic stroke (IS).
Thirty-six patients admitted with TIA (n = 14) or minor IS (n = 22) underwent transcranial Doppler evaluation and corneal confocal microscopy and were compared with 18 healthy controls.
Corneal nerve fiber density (P = 0.002), branch density (P = 0.004) and fiber length (P = 0.004) were significantly lower in patients with TIA or minor IS compared to controls, with no difference between patients with TIA and minor IS. Endothelial cell density (P = 0.003) was lower and endothelial cell area (P = 0.003) and perimeter (P = 0.006) were significantly higher in patients with TIA or minor IS compared to controls, with no difference between patients with TIA and minor IS. There were no differences in corneal nerve or endothelial cell morphology between patients with and without abnormal cerebrovascular reactivity. HbA1c was independently associated with CNFL, and endothelial cell polymegathism and pleomorphism were associated with both HbA1c and total cholesterol.
Corneal confocal microscopy identifies corneal nerve fiber loss and endothelial cell abnormalities in patients with TIA and minor IS and independent associations with HbA1c and cholesterol.
Stroke is associated with high fatality rates and major disability in survivors . Transient Ischemic Attack  and minor ischemic stroke (IS) share similar pathophysiology to stroke . Although, the ABCD2 score has been used to prognosticate the risk of subsequent stroke , a meta-analysis showed that it does not reliably discriminate patients at low or high risk of recurrent stroke . Similarly, neuroimaging may enhance the prognostic ability following TIA and minor stroke. However, recent analyses of patients with TIA or minor IS show that white matter lesions are associated with disability at 90 days, but not with stroke progression or stroke recurrence , and micro bleeds predict neither 90-day outcome or recurrence .
Forty patients with TIA or minor IS, aged between 18-80-year-old and able to provide consent were enrolled in the study. The diagnosis of TIA or minor ischemic stroke was confirmed clinically and radiologically by neurologists and neuroradiologists using AHA criteria . Patients with craniocerebral trauma, hypertensive encephalopathy, brain tumor, atrial fibrillation or taking anticoagulants were excluded. Three patients were excluded as they were found to be TIA mimics and one had cerebral venous sinus thrombosis. Thirty-six patients underwent Transcranial Doppler Ultrasound (TCD) and Corneal Confocal Microscopy (CCM). Ethical approvals were obtained from the Institutional Review Boards of Hamad General Hospital and Weill Cornell Medicine in Qatar.
This is the first study to demonstrate corneal nerve and endothelial cell pathology in patients with TIA or minor IS, extending our previous findings in patients with major stroke [19, 20]. Diabetes, hypertension, smoking, dyslipidemia [27–29], obesity  and metabolic syndrome  are known risk factors for stroke and are linked to cerebral white matter lesions and silent lacunar brain infarcts , but have limited prognostic value for recurrent stroke in patients with TIA and minor IS . Impaired cerebral reactivity has been associated with the risk of subsequent stroke in patients with TIA [32, 33], and smoking, hypertension, diabetes and cholesterol are related to altered CBF in patients with TIA and minor stroke [31, 34]. Endothelial dysfunction is involved in the pathophysiology of TIA  and lacunar stroke  and has been implicated in the development of silent lacunar infarcts and white matter lesions . It may also act as an independent predictor for a recurrent ischemic event [38, 39].